Cardiac manifestations of immediate hypersensitivity reactions to drugs will be investigated in isolated perfused hearts and in sub-human primates. The role of mediators such as histamine, SRS-A, and prostaglandins will be evaluated. The possibility that histamine release in the presence of digitalis is responsible for an interaction leading to severe cardiac dysfunction will be explored. Pharmacological means to alleviate cardiac dysfunction caused by histamine release will be sought. This investigation will involve "in vitro" and "in vivo" studies on the monkey heart undergoing anaphylactic reactions to penicillin antigens. Coronary perfusates will be assayed for released mediators. Cardiac function will be correlated with the amounts of mediator released in order to learn the significance of a particular release in anaphylaxis. This investigation should furnish a useful insight into the significance of the cardiac dysfunctions caused by histamine release. BIBLIOGRAPHIC REFERENCES: Levi, R., Ganellin, C.R., Allan, G. and Willens, H.J.: Selective impairment of atrioventricular conduction by 2-(2-pyridyl)ethylamine and 2-(2-thiazolyl)-ethylamine, two histamine H1-receptor antagonists. Europ. J. Pharmacol. 34: 237-240, 1975. Zavecz, J. H. and Levi, R.: Pharmacological characterization of the receptors mediating histamine-induced idioventricular tachyarrhythmias. Fed. Proc. 35: 2423, 1976 (Abstract).